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Microbiota and telomere shortening in gut-lung axis of human immunodeficiency virus infected donors Yang, Shun-Wei Julia


Previous studies have demonstrated the existence of a gut-lung axis and its proposed role in altering immune response and respiratory disease pathogenesis. The lung and gut microbiomes have been individually studied in the context of Human Immunodeficiency Virus (HIV) infection; however the gut-lung axis in HIV remains relatively unexplored and requires further investigation. This study examined the microbiomes of the gut-lung axis and telomere attrition in HIV subjects using paired human lung and small intestine tissue. Paired lung and small intestine tissue autopsy specimens were obtained from ART-treated HIV-positive and HIV-negative donors through the National NeuroAIDS Tissue Consortium. Frozen samples were sectioned on dry ice and weighed for DNA extraction using the QIAGEN DNeasy® Blood and Tissue kit. Droplet digital PCR was used to measure bacterial load and quantitative PCR was performed to determine absolute telomere length (aTL). The 16S rRNA V4 region was sequenced using the MiSeq sequencing platform. Extraction negatives were run through the entire workflow alongside samples for quality control. Raw sequence reads were processed using QIIME2 (Quantitative Insights Into Microbial Ecology 2, v2018.2) followed by statistical analysis using R studio. Several t-tests, linear regression, PERMANOVA and ANCOVA were used for statistical analysis. Microbial composition was not found to differ significantly between ART-treated HIV-positive and HIV-negative donors in both lung and small intestine. However, bacterial load and abundance of individual amplicon sequence variants (ASVs) were found to be correlated in the lung and small intestine. Bacteroides was decreased in ART-treated HIV-positive donors and identified as one of the bacteria most likely to help explain differences between HIV-negative and ART-treated HIV-positive microbiomes. Telomere length was demonstrated to be shortened in lungs of ART-treated HIV-positive donors in comparison to HIV-negative but no differences were found between the two groups in the small intestine. ART-treated HIV donors present microbiomes similar to HIV-negative donors, suggesting that ART can provide the microenvironment necessary to maintain a “healthy” microbiome. Furthermore, microbiomes of the gut-lung axis have demonstrated a correlation in bacterial load and abundance of individuals ASVs, suggesting a strong relationship between the two sites in both ART-treated HIV donors and HIV-negative donors.

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